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Antigens

Antigens. Jennifer Nyland, PhD Office: Bldg#1, Room B10 Phone: 733-1586 Email: jnyland@uscmed.sc.edu. Teaching objectives. To compare and contrast immunogen , antigen & hapten To describe the factors influencing immunogenicity To define the chemical nature of immunogens

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Antigens

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  1. Antigens Jennifer Nyland, PhD Office: Bldg#1, Room B10 Phone: 733-1586 Email: jnyland@uscmed.sc.edu

  2. Teaching objectives • To compare and contrast immunogen, antigen & hapten • To describe the factors influencing immunogenicity • To define the chemical nature of immunogens • To compare the structures of T-independent and T-dependent antigens • To introduce the concept of hapten-carrier conjugates and their structure • To characterize antigenic determinants • To define superantigens

  3. Overview of the immune system

  4. Initiation of immune response • Interaction between receptor and ligand • Affinity • Avidity Affinity: high low low strong binding strong binding weak binding

  5. Initiation of the immune response • Ligand-receptor binding context influences outcome No response Response A Response B

  6. Immunogen vs Antigen • Anything that induces specific immune response • Substance that reacts with product of immune system protein epitope

  7. Factors influencing immunogenicity

  8. Immunogenicity: contribution of immunogen • Foreignness • Size • Chemical composition • Primary structure --- sequence determinants • Secondary structure • Tertiary structure • Quarternary structure Conformational determinants

  9. Immunogenicity: contribution of immunogen • Foreigness • Size • Chemical composition • Physical form • Particular > Soluble • Denature > Native

  10. Immunogenicity: contribution of immunogen • Foreigness • Size • Chemical composition • Physical form • Degradability • Ag processing by Ag-presenting cells (APC)

  11. Immunogenicity: contribution of biological system • Genetics • Species • Individual • Responders vs Non-responders • Age

  12. Immunogenicity: method of administration • Dose • Route • Subcutaneous > Intravenous > Intragastric • Adjuvant • Substances that enhance immune response to Ag

  13. Chemical nature of immunogen • Proteins • Polysaccharides • Nucleic acids • Lipids • Some glycolipids and phospholipids can be immunogenic for T cells and illicit a cell-mediated immune response

  14. OH O Immunogenicity COO- Amino acids H3N+-C-H H Haptens Increasing immunogenicity Lipids Steroids Carbohydrates Tyr NO2 Proteins NO2

  15. Antigens: T-independent • Activate B cells without MHC class II T help • Polysaccharides • Properties • Polymeric structure • Polyclonal B cell activation, but poor memory • Resistance to degradation • Examples • Pneumococcal polysaccharide, LPS • Flagella

  16. Antigens: T-dependent • Require T help to activate B cells • Proteins • Structure • Examples • Microbial proteins • Non-self or altered-self proteins

  17. protein epitope Tyr Tyr NO2 NO2 NO2 NO2 NO2 NO2

  18. Hapten-carrier conjugates • Definition • Ag only if bound to carrier protein • Structure • Native determinants • Haptenic determinants

  19. Antigenic determinants recognized byB cells and Ab • Composition • Proteins, polysaccharides, nucleic acids, haptens • Sequence (linear) determinants • Conformational determinants • Size • 4-8 residues

  20. Antigenic determinants recongized byB cells and Ab • Composition • Size • Number • Limited (immunodominantepitopes) • Located on the external surface of the Ag (exposed)

  21. Antigenic determinants recognized byT cells • Composition • Proteins (some lipids) • Sequence determinants • Processed • MHC presentation (lipid presentation by MHC-like CD1) • Size • 8-15 residues • Number • Limited to those that can bind MHC

  22. Superantigens Ag T cell T cell • Definition • Polyclonal T cell response • Examples • Staphlycoccal enterotoxins • Toxic shock toxin TCR TCR SuperAg MHC MHC APC APC

  23. Summary of immune response • Adaptive immune response • Discrete determinants • Reacts with specific pathogen • Innate immune response • Broad molecular patterns • Reacts with a variety of pathogens

  24. Vocabulary • Immunogen • Antigen (Ag) • Hapten • Epitope or antigenic determinant • Antibody (Ab)

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